Drug & supplement interaction

Indian Long Pepper + Methotrexate

Methotrexate brand names: Rheumatrex, Otrexup, Rasuvo, Reditrex.

No Known Interaction
The bottom line No known interaction

We found no known interaction between Indian Long Pepper and Methotrexate in our sources. Absence of a documented interaction is not the same as proven safety, and does not guarantee one does not exist. Do not start, stop, or change a medication or supplement based on this page; confirm with your pharmacist or doctor first.

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Interaction report

Indian Long Pepper and Methotrexate

We checked these two against our interaction database. Here is what we found.

No Known Interaction Found

We did not find a documented interaction between Methotrexate and Indian Long Pepper in our sources. This does not guarantee that the combination is completely free of risk — there is often limited research on supplements and herbal products, especially around drug interactions.

If you decide to take both, the practical routine is simple: add one new thing at a time and note the date you started it. If the combination is going to disagree with you, it usually shows in the first days to a couple of weeks — and a start date turns “I’ve been feeling off” into something a pharmacist can actually work with. Do not stop a prescribed medicine on your own.

Always talk with your pharmacist or doctor before making changes to your medications or supplements, particularly if you take several medications or have an ongoing health condition.

Indian Long Pepper safety at a glance

Indian Long Pepper overall Use caution Likely fine as a food spice, but concentrated supplements lack strong safety data and piperine can affect how other substances are absorbed.
Pregnancy Avoid Medicinal amounts are not well studied and traditionally discouraged, so avoid supplement doses during pregnancy.
Breastfeeding Avoid There is not enough safety information, so avoid medicinal amounts while breastfeeding.

Safety guidance is general; always confirm with your pharmacist or doctor for your situation.

Still wondering about combining Methotrexate and Indian Long Pepper? Ask Dr. Brian Staiger, PharmD, BCPS directly ›
How we checked

Why No Interaction Is Listed for Methotrexate

Interactions in our licensed database are recorded against drug classes, not just single drug names. Methotrexate is filed under 6 classifications — including organic anion-transporting polypeptide substrates (oatp), organic anion transporter 3 (oat3) substrates, hepatotoxic drugs. Indian Long Pepper has documented interactions with 14 drug classes — the most serious being anticoagulant/antiplatelet drugs (moderate), antidiabetes drugs (moderate) and cyclosporine (neoral, sandimmune) (moderate) — and none of Methotrexate’s classifications are among them.

Classification data comes from our licensed Natural Medicines dataset. A medication can belong to classes beyond those recorded there, so this describes how the check was run — it is not a safety guarantee.

Keep it in perspective

Indian Long Pepper Does Interact With Other Medications

Indian Long Pepper has 893 moderate, 3 minor known drug interactions in our database — Methotrexate isn’t one of them. If you take anything else, check it against the full list below.

Taking anything else?

Check Another of Your Medications Against Indian Long Pepper

Covers the 2,830 medications we’ve checked against Indian Long Pepper. Pick one to open its full report.

What to actually watch for

What Methotrexate’s Own FDA Label Lists

This is not an interaction — none of it involves Indian Long Pepper. These are the most notable effects listed in the ADVERSE REACTIONS section of Methotrexate’s own FDA label, for the medication by itself. Knowing the drug’s own list makes it easier to work out the likely cause if something new turns up while you take both. 10 of them are worth acting on rather than waiting out — marked below.

  • Loss of vision Worth acting on
  • Bone thinning Worth acting on
  • Pain or burning when passing urine Worth acting on
  • Blood clots Worth acting on
  • Pancreatitis Worth acting on
  • A severe skin reaction Worth acting on
  • Seizures Worth acting on
  • Chest pain Worth acting on
  • A low platelet count Worth acting on
  • Kidney problems Worth acting on

Showing the 10 most notable of 45 label-listed effects — ranked by how unusual each one is across medicines generally, with serious effects weighted up.

From the ADVERSE REACTIONS section of the FDA label for Methotrexate. Read the label on DailyMed › Where a percentage is shown, it is the share of 489,806 voluntary FDA FAERS reports for Methotrexate that mention that effect — a reporting proportion, not an incidence rate and not evidence the drug caused it. Indian Long Pepper’s licensed record lists no adverse effects our clinical vocabulary could match, so there is no Indian Long Pepper side to compare — that is a limit of the record, not a statement that Indian Long Pepper has no side effects.

Overlapping uses

What Methotrexate Is Prescribed For, and What Indian Long Pepper Has Been Studied For

These two come up together because they touch the same health topic — not because they do the same job. Methotrexate is a prescription medicine with approved uses on its FDA label. Indian Long Pepper is a supplement: what follows is what researchers have looked at it for, and how strong that evidence is.

Methotrexate is prescribed for: Methotrexate treats a wide range of serious conditions. In cancer care, it is used for acute lymphoblastic leukemia, non-Hodgkin lymphoma, osteosarcoma, breast cancer, head and neck cancer, and gestational trophoblastic neoplasia (a rare tumor related to pregnancy). It is also used to prevent and treat meningeal leukemia (cancer affecting the lining of the brain and spinal cord). Outside of cancer, methotrexate is prescribed for adults with rheumatoid arthritis (RA), children with polyarticular juvenile idiopathic arthritis (a form of childhood arthritis), and adults with severe psoriasis that hasn't responded well to other treatments.

Indian Long Pepper has been studied for:

  • Psoriasis studied, not established Indian Long Pepper has been studied for this. Natural Medicines rates the evidence: Insufficient Reliable Evidence To Rate Read what the research shows

    Indian Long Pepper for psoriasis

    Although there has been interest in using oral Indian long pepper for psoriasis, there is insufficient reliable information about the clinical effects of Indian long pepper for this purpose.

  • Cancer studied, not established Indian Long Pepper has been studied for this. Natural Medicines rates the evidence: Insufficient Reliable Evidence To Rate Read what the research shows

    Indian Long Pepper for cancer

    Although there has been interest in using oral Indian long pepper for cancer, there is insufficient reliable information about the clinical effects of Indian long pepper for this purpose.

Effectiveness ratings and the research summaries above are the verbatim record from the Natural Medicines database, which grades evidence from “Effective” down to “Insufficient Reliable Evidence To Rate”. A rating below the top of that scale means researchers have looked at it — not that it works, and never that it can stand in for a prescribed medicine. Do not stop or replace Methotrexate on your own; if you are taking Indian Long Pepper for the same health topic, tell your prescriber, especially if the medicine is being adjusted to a target.

From our Q&A

Questions About Indian Long Pepper or Methotrexate

These are real questions from readers, answered by the pharmacists at HelloPharmacist — written by a person, not generated from a database. Each one covers Indian Long Pepper or Methotrexate, not necessarily both, but if one is close to what you were about to ask it will usually go further than a database entry can:

Not quite your question? Ask our pharmacists directly — it is free, there is no account required, and answers usually come back within 24 hours.

Everything else you take

See Every Supplement That Interacts With Methotrexate

This page covers Indian Long Pepper only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Methotrexate page lists 82 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Apple (major), Beer (major), Grapefruit (major) and Siberian Cocklebur (major).

By severity: 7 major · 60 moderate · 15 minor.

From our pharmacist’s overview on the Methotrexate page

“The liver is where methotrexate and supplements clash most. Methotrexate (Rheumatrex, Otrexup, Rasuvo), used for rheumatoid arthritis, psoriasis, and certain cancers, can strain the liver on its own, and 38 of the 82 interacting ingredients on this list add liver risk of their own, alcohol included, which makes this a list to approach…”

Reviewed by 2 · Jul 18, 2026

Open the Methotrexate interaction page

One more smart check

Taking Indian Long Pepper as Part of a Dietary Supplement Product? Check It for Interactions

We hold 597 real supplement products containing Indian Long Pepper, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Indian Long Pepper. Even though Indian Long Pepper itself has no known interaction with Methotrexate, another ingredient on your label might. Find your product and we’ll check every ingredient on its label:

How much people look this up

Where Indian Long Pepper and Methotrexate Sit Against Everything Else

Out of every supplement and medication people look up on HelloPharmacist, here is where these two land this week — and which way each has been moving.

Supplement Indian Long Pepper
Top 25%

#203 of 1,452 supplements looked up here in the last 7 days

29 days ago today
Medication Methotrexate
Top 5%

#49 of 2,830 medications looked up here in the last 7 days

29 days ago today

Position among everything looked up on this site, not a measure of how commonly either one is used or how important it is. A supplement can climb this list because of a news story. It counts every request to the page, automated ones included, and nothing here identifies anyone.

Where does our data come from?
  • Source: the Natural Medicines (TRC Healthcare) clinical database — the evidence-graded professional reference for herb & supplement interactions.
  • Citation library: 103,510 references behind our interaction content, 65,311 of them resolved to verified PubMed/DOI sources. See every Indian Long Pepper reference on this page ↓
  • Freshness: we automatically re-check this combination every week — this pair was last verified September 13, 2026. The Indian Long Pepper and Methotrexate records this page draws on were last updated June 22, 2026.
  • What “no known interaction” means: no documented interaction in the sources above — not a guarantee of safety. Supplements are studied far less than prescription drugs, so we say exactly what the evidence supports, and nothing more.
Data structure & sourcing designed and verified by .
Supplement

About Indian Long Pepper

What is Indian Long Pepper?

Indian Long Pepper
  • Digestive upset
  • Respiratory and cough complaints
  • Boosting absorption of other supplements
  • Pain and inflammation
  • General wellness in Ayurveda

Indian long pepper (pippali) is a spice long used in Ayurvedic medicine and is best known for its piperine content, which may increase how well the body absorbs certain other substances. Modern human research on its health benefits is limited, so use it cautiously and let your pharmacist or doctor know if you take it regularly.

Piper longum · Piperaceae · Dried fruit (and sometimes the root) · Dried fruit (spice), powder, capsules, extracts, and traditional Ayurvedic formulas

An interaction check asks whether these two react with each other — it does not ask whether Indian Long Pepper is a good idea for someone in your situation. Here is what our Indian Long Pepper record says about it on its own.

Indian Long Pepper: dosing

There is no well-established standard dose of Indian long pepper for any health condition. Traditional Ayurvedic use and modern supplement products vary widely.The safest approach is to follow the directions on the product label and not exceed them.

From our Indian Long Pepper monograph — the full record covers uses, side effects and every documented interaction.

Read the full Indian Long Pepper monograph & all interactions
Medication

About Methotrexate

What Is Methotrexate Used For?

Brand names: Rheumatrex, Otrexup, Rasuvo, Reditrex

Methotrexate treats a wide range of serious conditions. In cancer care, it is used for acute lymphoblastic leukemia, non-Hodgkin lymphoma, osteosarcoma, breast cancer, head and neck cancer, and gestational trophoblastic neoplasia (a rare tumor related to pregnancy). It is also used to prevent and treat meningeal leukemia (cancer affecting the lining of the brain and spinal cord).

Outside of cancer, methotrexate is prescribed for adults with rheumatoid arthritis (RA), children with polyarticular juvenile idiopathic arthritis (a form of childhood arthritis), and adults with severe psoriasis that hasn't responded well to other treatments.

Most-Reported Side Effects for Methotrexate

From FAERS, the FDA’s public side-effect reporting system (489,806 reports, all brands). Reports are voluntary and are not proof the drug caused the effect.

Rheumatoid arthritis 42,798 reports
Arthralgia 40,830 reports
Fatigue 33,049 reports
Nausea 28,999 reports
Joint swelling 25,026 reports
See full Methotrexate drug information
Keep checking

Other Drugs & Indian Long Pepper

Browse every other medication we’ve checked against Indian Long Pepper — both the ones with a known interaction and the ones without. Select any drug for the full detail.

0Major
893Moderate
3Minor
1,933No known interaction
Moderate

893 interactions

Showing 60 of 893 moderate interactions — see all 893 on the Indian Long Pepper page.

Minor

3 interactions

No interaction 1,933 drugs checked — show the list
Evidence & sources

Indian Long Pepper References

The 12 references that drive our Indian Long Pepper monograph and interaction data, from the evidence-graded Natural Medicines (TRC Healthcare) database. Citations with a link open the study on PubMed or the publisher’s site.

  1. Bano G, Amla V, Raina RK, et al. The effect of piperine on pharmacokinetics of phenytoin in healthy volunteers. Planta Med 1987;53:568-9. PubMed
  2. Bano G, et al. Effect of piperine on bioavailability and pharmacokinetics of propranolol and theophylline in healthy volunteers. Eur J Clin Pharmacol 1991;41;615-7. PubMed
  3. Bhardwaj RK, Glaeser H, Becquemont L, et al. Piperine, a major constituent of black pepper, inhibits human P-glycoprotein and CYP3A4. J Pharmacol Exp Ther 2002;302:645-50. PubMed
  4. Pattanaik S, Hota D, Prabhakar S, et al. Pharmacokinetic interaction of a single dose of piperine with steady-state carbamazepine in epilepsy patients. Phytother Res 2009;23:1281-6.
  5. Kasibhatta, R. and Naidu, M. U. Influence of piperine on the pharmacokinetics of nevirapine under fasting conditions: a randomised, crossover, placebo-controlled study. Drugs R.D. 2007;8(6):383-391. PubMed
  6. Mujumdar, A. M., Dhuley, J. N., Deshmukh, V. K., Raman, P. H., Thorat, S. L., and Naik, S. R. Effect of piperine on pentobarbitone induced hypnosis in rats. Indian J Exp.Biol. 1990;28(5):486-487.
  7. Panda, S. and Kar, A. Piperine lowers the serum concentrations of thyroid hormones, glucose and hepatic 5'D activity in adult male mice. Horm.Metab Res. 2003;35(9):523-526. PubMed
  8. Hiwale, A. R., Dhuley, J. N., and Naik, S. R. Effect of co-administration of piperine on pharmacokinetics of beta-lactam antibiotics in rats. Indian J Exp.Biol. 2002;40(3):277-281.
  9. Han, Y., Chin Tan, T. M., and Lim, L. Y. In vitro and in vivo evaluation of the effects of piperine on P-gp function and expression. Toxicol.Appl.Pharmacol. 8-1-2008;230(3):283-289. PubMed
  10. Sharma, P., Varma, M. V., Chawla, H. P., and Panchagnula, R. In situ and in vivo efficacy of peroral absorption enhancers in rats and correlation to in vitro mechanistic studies. Farmaco 2005;60(11-12):874-883. PubMed
  11. Zutshi, R. K., Singh, R., Zutshi, U., Johri, R. K., and Atal, C. K. Influence of piperine on rifampicin blood levels in patients of pulmonary tuberculosis. J Assoc.Physicians India 1985;33(3):223-224.
  12. Yadav V, Krishnan A, Vohora D. A systematic review on Piper longum L.: Bridging traditional knowledge and pharmacological evidence for future translational research. J Ethnopharmacol. 2020;247:112255. PubMed

Medication overviews come from MedlinePlus (NIH); supplement label data from the NIH Dietary Supplement Label Database. Content is written and reviewed by licensed HelloPharmacist pharmacists — see our data sources and editorial standards.

Pharmacist Counseling Corner

Taking Indian Long Pepper and Methotrexate Together: Common Questions

Is it safe to take Indian Long Pepper with Methotrexate?
We do not list a known interaction between Indian Long Pepper and Methotrexate. That does not guarantee the combination is risk-free, so confirm with your pharmacist or doctor — especially if you take other medications or have a health condition.
Are Indian Long Pepper and Methotrexate used for the same thing?
They overlap in purpose, which usually means the real question is whether you need both rather than whether they are safe together. This page lists the shared uses and how strong the evidence is for Indian Long Pepper in each. That is a conversation for your prescriber, especially if Methotrexate is being adjusted to a target.
How was the Indian Long Pepper and Methotrexate combination checked?
Interactions in our licensed database are recorded against drug classes. Methotrexate is filed under 6 classifications, and Indian Long Pepper has documented interactions with 14 drug classes — none of Methotrexate's classifications are among them. A medication can belong to classes beyond those recorded in our dataset, so this describes how the check was run rather than guaranteeing safety.
Does Indian Long Pepper interact with any other medications?
Yes. Indian Long Pepper has 896 documented drug interactions in our database — Methotrexate is simply not one of them. If you take anything else, it is worth checking each one; they are all listed on this page.
Does Methotrexate interact with any supplements?
Yes. Methotrexate has documented interactions with 82 supplements in our database — Indian Long Pepper is not one of them. The Methotrexate interaction page linked on this page lists every one, ranked by severity.

Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy

Still Have a Question About Methotrexate and Indian Long Pepper?

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This information is for education only and is not a substitute for professional medical advice. Always check with your pharmacist or doctor before starting, stopping, or combining supplements and medications.